Process for the accelerated obtaining of terpenic oxides using ultraviolet light

ABSTRACT

A process for the preparation of verbenone, myrtenol, myrtenal, trans-verbenol, cis-verbenol, pinocarveol, 3.01-2 pinene, Alpha -pinene epoxide and campholene aldehyde comprising I. subjecting oil of turpentine to an intense oxidation step comprising continuously insufflating air through said oil at a temperature of about 70* C while agitating said oil and irradiating said oil with ultraviolet light in the presence of A. FROM 0.05 TO 0.5 PERCENT BY WEIGHT OF A PROMOTER SELECTED FROM THE GROUP CONSISTING OF ORGANIC SALTS AND COMPLEXES OF NICKEL, VANADIUM, TUNGSTEN, TANTALUM, NIOBIUM, RHENIUM, TELLURIUM AND SELENIUM; AND B. IN THE PRESENCE OF FROM 1 TO 10 PERCENT BY WEIGHT OF AT LEAST ONE CATALYST SELECTED FROM THE GROUP CONSISTING OF 1. THE ABIETATES, THE LEVOPIMARATES, THE DEXTROPIMARATES AND THE PINONATES OF COBALT, MANGANESE AND NICKEL; AND 2. A MEMBER SELECTED FROM THE GROUP CONSISTING OF THE ACETYLACETONATES, THE PHTHALOCYANINES AND THE TERPENIC ACID SALTS OF NICKEL, COBALT, VANADIUM, TUNGSTEN, TANTALUM, NIOBIUM AND RHENIUM; THE OXIDES OF SELENIUM AND TELLURIUM; THE NAPHTHENATES, THE OLEATES, AND THE STEARATES OF COBALT, MANGANESE AND NICKEL; IN THE PRESENCE OF FROM 0.05 TO 0.5 PERCENT BY WEIGHT OF AT LEAST ONE MEMBER SELECTED FROM THE GROUP CONSISTING OF COPPER (II) salts, cesium salts and mixtures thereof; II. distilling off the reaction products having a boiling point of about 75* C at 10 mmHg; and III. rectifying the distilled reaction products collected, is disclosed.

United States Patent Muller 1 June 27, 1972 [72] Inventor: PierreMuller, Nanterre, France [73] Assignee: Laboratories De LOzothine,Nanterre,

France 22 Filed: Feb. 14,1969

[21] Appl.No.: 799,520

FOREIGN PATENTS OR APPLICATIONS 1,097,1 18 12/1967 Great Britain..260/675.5

Primary ExaminerBenjamin R. Padgett Assistant Examiner-Harvey E. BehrenAttorney-Sughrue, Rothwell, Mion, Zinn & Macpeak [5 7] ABSTRACT Aprocess for the preparation of verbenone, myrtenol, myrtenal,trans-verbenol, cis-verbenol, pinocarveol, 3.01-2

pinene, a-pinene epoxide and campholene aldehyde comprismg I. subjectingoil of turpentine to an intense oxidation step comprising continuouslyinsufilating air through said oil at a temperature of about 70 C whileagitating said oil and irradiating said oil with ultraviolet light inthe presence of a. from 0.05 to 0.5 percent by weight of a promoterselected from the group consisting of organic salts and complexes ofnickel, vanadium, tungsten, tantalum, niobium, rhenium, tellurium andselenium; and

b. in the presence of from 1 to 10 percent by weight of at least onecatalyst selected from the group consisting of l. the abietates, thelevopimarates, the dextropimarates and the pinonates of cobalt,manganese and nickel; and

2. a member selected from the group consisting of the acetylacetonates,the phthalocyanines and the terpenic acid salts of nickel, cobalt,vanadium, tungsten, tantalum, niobium and rhenium; the oxides ofselenium and tellurium; the naphthenates, the oleates, and the stearatesof cobalt, manganese and nickel; in the presence of from 0.05 to 0.5percent by weight of at least one member selected from the groupconsisting of copper (ll) salts, cesium salts and mixtures thereof;

ll. distilling ofi the reaction products having a boiling point ofabout75 C at 10 mmI-lg; and

Ill. rectifying the distilled reaction products collected, is disclosed.

2 Claims, No Drawings PROCESS FOR THE ACCELERA'I'ED OBTAINING OFTERPENIC OXIDES USING ULTRAVIOLET LIGHT The present invention concerns anew process for obtaining terpenic oxides and, in particular, verbenone,Myrtenol, Myrtenal, Trans-verbenol, Cis-verbenol, Pinocarveol, 3.01-2Pinene.

Terpenic oxides have long been used in veterinary and humantherapeutics, but their preparation from oxidation processes of theconstituents of the natural oils of turpentine makes it essential thatthe oxidation operations should be carried out very delicately. Thevarious conventional processes are long, complicated and difficult.Moreover, these processes result in terpenic oxides containing variouscontents of nonhydrosoluble bodies which it is necessary to eliminate bychemical means. The hydroperoxides formed in the course of theseprocesses have therefore to be eliminated in the course of a subsequentoperation.

The present invention therefore concerns a new, simple, rapid andeconomical process for obtaining the following compounds: verbenone,myrtenol, myrtenal, trans-verbenol, cis-verbenol, pinocarveol, 3.01-2pinene, a pinene epoxide, campholene aldehyde, characterized in thatturpentine oil is subjected to an intense oxidation phase in thepresence of the combination of at least one promoter selected from theorganic salts or complexes of the following metals or metalloids:nickel, vanadium, tungsten, tantalium, niobium, rhenium, selenium ortellurium and at least on catalyst selected from the following groupabietate or levopimarate or dextropimarate or pinonate of cobalt ormanganese or nickel, this phase being followed by a fractionateddistillation by selection of products distilling above 75 under apressure of mm mercury, then a final phase of rectification by selectionof products collected between 72 and 75 under 5 mm mercury.

Another object of the invention is to combine the action of thepromoter-catalyst combination with continuous insufflation by a largesupply of compressed air, the joint action of ultra-violet radiation,strictly constant and strong agitation and the maintaining of thetemperature of the oil of turpentine at 70 during the entire oxidationphase.

Another object of the invention is to obtain a more constant yield,whilst extending the choice of the aforementioned catalysts to thefollowing catalysts: acetyl-acetonates and phthalo-cyanines of nickel,cobalt, vanadium, tungsten, tantalium, niobium, rhenium, oxides ofselenium or tellurium, naphthenates, oleates and stearates of metalssuch as cobalt or manganese or nickel in combining them with one of theaforementioned promoters in the presence of promoters: salts of Cwand/or cesium.

In this manner a reliable, rapid and economical process is obtained, theadvantages and features of which will be apparent from the followingdescription:

According to the invention, the first phase or intense oxidation phaseof the oil of turpentine is characterized by all the followingconditions:

a. Continuous insufflation with a large supply of compressed air,

. Action of light and particularly ultra-violet radiation,

c. The raising and maintaining of the temperature of the oil ofturpentine at 70,

d. Constant agitation of the products by means of an agitator rotatingat 3,200 revolutions per minute, for example,

e. The presence, in a concentration of l l0 percent of the total weightof one of the afore-mentioned oxidation catalysts, nickel pinonate, forexample. Nickel pinonate may be obtained by mixing 18.5 g pinonic acidand 4 g sodium in flakes in 25 ml water. Sodium pinonate is formed. Thena solution is added containing 24 g nickel chloride (Cl Ni, 6 CHdissolved in ml water: nickel pinonate is precipitated. It is sufficientto collect it by filtration and to dry it in vacuo,

f. The presence, in a concentration of 0.05 to 0.5 percent, of

at least one of the salts or organic complexes of the following metalsor metalloides Nickel, vanadium, tungsten tantalium, niobium, rhenium,selenium or tellurium, for example: selenium oxide.

These operating conditions make it possible to assist the oxidationreactions whilst destroying the undesirable hydroperoxides, thusavoiding the subsequent destruction operation by chemical means whichwas necessary in previous processes. Moreover, a maximum amount ofterpenic oxides is obtained in a relatively very short period, since itcorresponds to a reduction of time of the order of percent compared withprevious processes or, to underline the point, less than 40 hoursinstead of 8 to 10 days.

Furthermore, this result was discovered without expecting that under theeffect of this intense oxidation with destruction of the undesirablehydroperoxides, the phenomena of thermal decomposition being produced inthe course of distillation are completey reduced and that the acidity ofthe products obtained and the quantity of tars formed in thedistillation vat are minimal. Consequently only a single distillation isnecessary to obtain products capable of being directly used inpharmaceutical therapeutics.

The second phase thus corresponds to a single fractionated distillationunder reduced pressure of the oxidized oil of turpentine. Theuntransformed a and )3 pinenes are first distilled and then the fractionis collected which distills above 75 under pressure of 10 mm mercury.

It should be noted that the product collected may be immediately used inall pharmaceutical forms with the exclusion of the injectable solutionsand that the processes of purifica tion by chemical means required withprevious methods are avoided.

The third phase is intended for the obtaining of practically neutralterpenic oxides, enriched with carbonyl derivatives, which can bedirectly employed in pharmaceutical therapeutics, either in a pure stateor in a state combined with various compounds. The product, pure orcombined, may be used in all its forms, including injectable solutionsintended for intramuscular or intra-venous administration.

For this purpose, the fraction previously isolated in the course of thesecond phase, is rectified between 72 and 75 under a reduced pressure of5 mm mercury. A product is collected which no longer needs to bechemically treated.

The present invention thus makes it possible to obtain, by a rapid,economical and reliable process, terpenic oxides enriched or notenriched with carbonyl products and capable of use immediately inpharmaceutical therapeutics.

However, according to the present invention it is possible to replacenickel pinonate with cobalt or manganese pinonate or by the following:levopimarate, dextropimarate, cobalt, nickel or manganese abietate.

Similarly, in order to improve the regularity of the operations and toobtain a constant yield, it is possible to use, in addition to theaforementioned catalysts, terpenic acid salts, acetyl-acetonates andphthalo-cyanines of nickel, cobalt, vanadium, tungsten, tantlium,niobium, rhenium, oxides of selenium or tellurium, tantalium, oleatesand stearates of metals such as cobalt or manganese or nickel, combiningthem with one of the afore-mentioned promoters in the presence of thepromoters: salts of Cu and/or cesium, the concentration of the promotersCu and cesium also varying from 0.05 to 0.5 percent.

Thus, starting from an oil or essence of turpentine, called Bordeauxessence, comprising as constituents: approximately 70 29 percent of 01pinene and approximately 25 percent of B pinene, the following mixtureresults: verbenone 25 to 30 percent, myrtenol and pinocarveol 7 to l2percent, myrtenal 5 to 6 percent, trans-verbenol, cis-verbenol and3.01-2 pinene, 45-50 percent, pinene epoxide and campholene aldehyde, 5percent.

These bodies were obtained by selecting, as catalysts, nickel pinonatein the presence of copper sulphate with respective concentration of 10percent and 0.1 percent.

Similar results were obtained by selecting cobalt abietate as catalystsat a rate of 8 percent and nickel pinonate as promoter: 0.3 percent.

Similarly it was possible to replace cobalt abietate in the foregoingexample by acetyl-acetonate of cobalt: 5 percent, by

using as promoter a 0.3 percent nickel pinonate in the presence of 0.1percent copper sulphate.

Tests have shown that from the start of this oxidation phase,hydroperoxides are formed on the ethylene compounds and peroxides on thealdehyde functions or ketones produced in the medium. These peroxidesmay act on the campholene aldehyde to give radical cyclizations leadingto ketones of the camphor or dihydrocamphenone type which are formed ina very small quantities.

in addition to the acceleration of the oxidation reactants and thedestruction of the hydroperoxides a regularization of the reactions wasdiscovered ensuring a yield from the operations which is both better andmore constant.

After oxidation and in the course of the following phase of fractionateddistillation under reduced pressure the phenomena of thermaldecomposition are reduced with the result that the residues formed inthe distillation vat appear in only very small quantities. Only theproducts are eliminated which are first distilled and which containpinenes which have not yet been oxidized, as also a small quantity offormic acid and acetic acid, formed in the course of the precedingoxidation operation. Then the fraction is collected which distills above75 under a pressure of 10 mm mercury. The action of the alreadymentioned catalysts with one or more aforesaid promoters, makes itpossible to reduce to the minimum the reject from the initialdistillation. In this manner the above-listed bodies are obtained, theterpenic products of resinification which are unsuitable forpharmaceutical use remaining in the distillation vat.

Finally, greater speed is achieved in the transformation of the essencesof oxygenated terpenic derivatives, a more complete transformation, amore constant yield and, during the distillation, a greater quantity ofproducts capable of direct use in pharmaceutical therapeutics.

What we claim is:

l. A process for the preparation of verbenone, myrtenol, myrtenal,trans-verbenol, cis-verbenol, pinocarveol, 3.012.0 pinene, a-pineneoxide and campholene aldehyde, which comprises:

1. subjecting oil of terpentine to an intense oxidation step, whichcomprises continuously insufflating air through said oil at atemperature of about C., while agitating said oil and irradiating saidoil with ultraviolet light in the presence of from 1.0 to 10.0 percent,by weight, of a catalyst selected from the group consisting of theabietates, levopimarates, dextropimarates, and pinonates of cobalt,manganese and nickel, 0.3 percent, by weight, of one of theaforementioned abietates, levopimarates, dextropimarates and pinonatesof nickel, as a promoter, and from 0.05 to 0.5 percent of a secondpromoter selected from the group consisting of a copper (ll) salt and acesium salt,

2. distilling off the reaction products having a boiling point ofaboutC. at 10 mm Hg, and

3. rectifiying the distilled reaction products collected.

2. The process of claim 1, wherein said catalyst members are replaced bya member selected from the group consisting of the acetylacetonates,phthalocyanines, and terpenic acid salts of nickel, cobalt, vanadium,tungsten, tantalum, niobium and rhenium, the oxides of selenium andtellurium, and the naphthenates, oleates and stearates of cobalt,manganese and nickel.

1. SUBJECTING OIL OF TURPENTINE TO AN INTENSE OXIDATION STEP COMPRISINGCONTINUOUSLY INSUFFLATING AIR THROUGH SAID OIL AT A TEMPERATURE OF ABOUT70*C WHILE AGITATING SAID OIL AND IRRADIATING SAID OIL WITH ULTRAVIOLETLIGHT IN THE PRESENCE OF A. FROM 3.05 TO 0.5 PERCENT BY WEIGHT OF APROMTER SELECTED FROM THE GROUP CONSISTING OF ORGANIC SALTS ANDCOMPLEXES OF NICKEL, VANADIUM, TUNGSTEN, TANTALUM, NIOBIUM, RHENIUM,TELLURIUM AND SELENIUM; AND B. IN THE PRESENCE OF FROM 1 TO 10 PERCENTBY WEIGHT OF AT LEAST ONE CATALYST SELECED FROM THE GROUP CONSISTINGOF
 1. THE ABIETATES, THE LEVOPIMARATES, THE DEXTROPIMARATES AND THEPINONATES OF COBALT, MANGANESE AND NICKEL; AND
 2. A MEMBER SELECTED FROMTHE GROUP CONSISTING OF THE ACETYLACETONATES, THE PHTHALOCYANINES ANDTHE TERPENIC ACID SALTS OF NCKEL, COBALT, VANADIUM, TUNGSTEN, TANTALUM,NIOBIUM AND RHENIUM; THE OXIDES OF SELENIUM AND TELLURIUM; THENAPTHENATES, THE OLEATES, AND THE STEARATES OF COBALT, MANGANESE ANDNICKEL; IN THE PRESENCE OF FROM 0.05 TO 0.5 PERCENT BY WEIGHT OF ATLEAST ONE MEMBER SELECTED FROM THE GROUP CONSISTING OF COPPER (II)SALTS, CESIUM SALTS AND MIXTURES THEREOF; II. DISTILLING OFF THEREACTION PRODUCTS HAVING A BOILING POINT OF ABOUT 75*C AT 10 MMHG; ANDIII. RECTIFYING THE DISTILLED REACTION PRODUCTS COLLECTED, IS DISCLOSED.2. distilling off the reaction products having a boiling point of about75* C. at 10 mm Hg, and
 2. The process of claim 1, wherein said catalystmembers are replaced by a member selected from the group consisting ofthe acetylacetonates, phthalocyanines, and terpenic acid salts ofnickel, cobalt, vanadium, tungsten, tantalum, niobium and rhenium, theoxides of selenium and tellurium, and the naphthenates, oleates andstearates of cobalt, manganese and nickel.
 3. rectifiying the distilledreaction products collected.